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Optimizing the diagnosis and management of ductal prostate cancer

Abstract

Ductal adenocarcinoma (DAC) is the most common variant histological subtype of prostate carcinoma and has an aggressive clinical course. DAC is usually characterized and treated as high-risk prostatic acinar adenocarcinoma (PAC). However, DAC has a different biology to that of acinar disease, which often poses a challenge for both diagnosis and management. DAC can be difficult to identify using conventional diagnostic modalities such as serum PSA levels and multiparametric MRI, and the optimal management for localized DAC is unknown owing to the rarity of the disease. Following definitive therapy for localized disease with radical prostatectomy or radiotherapy, the majority of DACs recur with visceral metastases at low PSA levels. Various systemic therapies that have been shown to be effective in high-risk PAC have limited use in treating DAC. Although current understanding of the biology of DAC is limited, genomic analyses have provided insights into the pathology behind its aggressive behaviour and potential future therapeutic targets.

Key points

  • Ductal adenocarcinoma (DAC) is the most common variant histological subtype of prostate carcinoma, which has a unique and aggressive biology.

  • In contrast to prostatic acinar adenocarcinoma (PAC), the majority of DACs present with lower urinary tract symptoms, have a low serum PSA and are often clinically under-staged.

  • DAC tends to present with advanced disease and has poor outcomes with surgery or radiotherapy compared with high-risk PAC. Multimodal therapies are often needed upfront when treating localized DAC.

  • The genomic makeup of DAC resembles castration-resistant PAC and warrants aggressive therapy, including the use of upfront use of novel systemic or combination therapies in neoadjuvant, adjuvant and metastatic settings.

  • Aggressive surveillance post-radical therapy for localized disease with imaging, including CT of the chest, is warranted, as patients with DAC develop bony and visceral metastases at low PSA levels.

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Fig. 1: Histopathology of ductal adenocarcinoma of the prostate.
Fig. 2: Histopathology of intraductal carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia.
Fig. 3: Ductal adenocarcinoma involving the urethra.
Fig. 4: Metastatic ductal adenocarcinoma of the prostate.
Fig. 5: Multiparametric MRI of ductal adenocarcinoma and acinar-type adenocarcinoma of the prostate.
Fig. 6: Involvement of adjacent structures with locally advanced ductal adenocarcinoma of the prostate.

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Acknowledgements

The authors thank Patricia Troncoso, Department of Pathology, University of Texas, MD Anderson Cancer Center, for input with proofreading of the manuscript before submission, and the medical illustrator, Kelly Kage from the Division of Diagnostic Imaging, MD Anderson Cancer Center.

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W.R. researched data for the article, W.R., D.D.S., T.B., M.Z., C.T. and B.F.C. made a substantial contribution to discussion of the content of the article, W.R., D.D.S. and M.Z. wrote the article and D.D.S., T.B., M.Z., N.N., T.C.T., B.B., A.A., S.-M.T., C.T., J.W.D., L.P. and B.F.C. reviewed the manuscript before submission.

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Correspondence to Weranja Ranasinghe.

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Nature Reviews Urology thanks A. Antonelli, T. Bismar, L. Egevad and D. Murphy for their contribution to the peer review of this work.

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Glossary

Amphophilic cytoplasm

Cell cytoplasm stains with both basic and acidic dyes on histology staining.

Endometrial tumour

A tumour that originates from the endometrial lining of the uterus. Ductal adenocarcinoma of the prostate was originally thought to histologically resemble an endometrial tumour.

Prostate-specific membrane antigen

(PSMA). A prostate-specific transmembrane protein that is overexpressed in prostate cancers.

Ki-67 proliferation index

A marker of cell proliferation where higher levels are associated with more aggressive tumours.

Mullerian vestige

Non-functional remnants of embryological Mullerian ducts that give rise to the female organs (vagina, uterus and fallopian tubes) and regresses in males.

KEGG pathway analysis

A compilation of genomic, biological, disease and chemical databases and is used in bioinformatics analyses including identification of biological pathways associated with different genes.

Mismatch repair mutations

Mutations of genes that repair mis-paired bases after DNA replication, which results in biosynthetic errors and tumour development.

cGAS–STING pathway

A central cellular cytosolic double-stranded DNA sensor, allowing innate immune response to infections, inflammation and cancer.

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Ranasinghe, W., Shapiro, D.D., Zhang, M. et al. Optimizing the diagnosis and management of ductal prostate cancer. Nat Rev Urol (2021). https://doi.org/10.1038/s41585-021-00447-3

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